The present invention relates to systems and methods for attaining resolution in light microscopy beyond the diffraction limit.
In traditional optical microscopy, the resolution of an image is limited by the Abbe criterion, which states that the smallest detail that can be resolved has a size of ˜λ/2. This criterion is based on the shape of the Point-Spread Function (PSF) of the optical system, which is the shape of a point-like source that is imaged by the system. The resolution limitation impairs the ability to obtain structural information for biological molecules such as DNA, RNA, and proteins, whose relevant dimensions scale to a few nanometers.
Various methods have been developed in cell biology to image cellular structures with sub-wavelength resolution. However, among the shortcomings include the fact that the resolution in several of these methods is limited by the signal-to-noise ratio (SNR), which is determined primarily by the position-localization error of single-molecule detection.
Thus, improved methods for sub-wavelength optical microscopy are needed, including methods for reducing the position-localization error of single-molecule detection.